Quantification of the binding potential of cell-surface receptors in fresh excised specimens via dual-probe modeling of SERS nanoparticles.

Quantification of the binding potential of cell-surface receptors in fresh excised specimens via dual-probe modeling of SERS nanoparticles.
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DOI:
10.1038/srep08582
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发表时间:
2015-02-26
期刊:
影响因子:
4.6
通讯作者:
Tichauer KM
Tichauer KM
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Sinha L;Wang Y;Yang C;Khan A;Brankov JG;Liu JT;Tichauer KM

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完全切除癌组织是外科肿瘤学的中心目标,但在某些情况下难以实现,特别是当必须最小化周围正常组织的切除时。因此,当术后病理学发现手术边缘有残留肿瘤时,通常需要再次切除手术。术中肿瘤边缘评估的方法,不敏感的非特异性来源的分子探针的积累和对比度,采用动力学建模分析的双探针染色使用表面增强拉曼散射纳米粒子(Sers NPs)。将人神经胶质瘤(U251)和表皮样瘤(A431)皮下植入6只无胸腺小鼠中。新鲜切除的组织用表皮生长因子受体(EGFR)靶向和非靶向Sers NP的等摩尔混合物染色。结合电位(BP;与受体浓度成比例)的EGFR --与癌症相关的细胞表面受体--从响应于系列冲洗的靶向和非靶向NP浓度的动力学建模来估计。健康、U251和A431组织中的EGFR BP分别为0.06 ± 0.14、1.13 ± 0.40和2.23 ± 0.86,这与流式细胞术测量和已发表的报告一致。这种方法能够量化新鲜组织中细胞表面生物标志物的BP,这为术中分析肿瘤边缘提供了一种准确的新方法。
The complete removal of cancerous tissue is a central aim of surgical oncology, but is difficult to achieve in certain cases, especially when the removal of surrounding normal tissues must be minimized. Therefore, when post-operative pathology identifies residual tumor at the surgical margins, re-excision surgeries are often necessary. An intraoperative approach for tumor-margin assessment, insensitive to nonspecific sources of molecular probe accumulation and contrast, is presented employing kinetic-modeling analysis of dual-probe staining using surface-enhanced Raman scattering nanoparticles (SERS NPs). Human glioma (U251) and epidermoid (A431) tumors were implanted subcutaneously in six athymic mice. Fresh resected tissues were stained with an equimolar mixture of epidermal growth factor receptor (EGFR)-targeted and untargeted SERS NPs. The binding potential (BP; proportional to receptor concentration) of EGFR – a cell-surface receptor associated with cancer – was estimated from kinetic modeling of targeted and untargeted NP concentrations in response to serial rinsing. EGFR BPs in healthy, U251, and A431 tissues were 0.06 ± 0.14, 1.13 ± 0.40, and 2.23 ± 0.86, respectively, which agree with flow-cytometry measurements and published reports. The ability of this approach to quantify the BP of cell-surface biomarkers in fresh tissues opens up an accurate new approach to analyze tumor margins intraoperatively.
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